News (Updated August 13, 2005)

[Home]  [
Previous news]


New HIV Treatment Strategy Shows Promise

By EMMA ROSS, AP Medical WriterSat Aug 13, 9:54 AM ET

A new treatment strategy has shown promise in helping to transform HIV into a curable infection. Preliminary research published this week in The Lancet medical journal outlines how scientists used an anti-convulsant drug to awaken dormant HIV hiding in the body, where it is temporarily invisible but still dangerous.

HIV infection is incurable because current drugs only work when the virus is multiplying, which occurs only when it is in an active cell. However, HIV sometimes infects dormant cells, and when it does, it becomes dormant itself.

While the virus poses no threat in its resting state, the sleeping cells sporadically wake up, reactivating the virus and causing it to multiply. Patients must continue to take medications for the rest of their lives so they can fight the virus when it comes out of the reawakened cells. Only if every last infected dormant cell is wiped out — or the virus purged from these cells — can patients stop taking medication and be virus-free, experts say.

Figuring out how to clear this reservoir of latent infection, or whether that's even possible, is one of the hottest areas of AIDS research.

Over the last few years, a handful of drugs have been shown to decrease the size of the dormant HIV pool, but they were subsequently abandoned because their effect was either too weak or the side effects too toxic.

The latest drug, valproic acid, shows more promise, said Dr. Warner Greene, director of the Gladstone Institute for Virology and Immunology at the University of California, San Francisco.

"It's a first baby step, showing that maybe the use of (this type of drug) — far more likely in combination with one or two other agents — might be a viable approach for tackling this latency problem," said Greene, who was not involved with the research but is conducting similar studies.

"The idea, if we could ever do it, is to purge every latently infected cell. Treat patients for probably two or three years, they'd be able to come off their antiretroviral therapy and they'd be virus-free," he said.

The study, led by Dr. David Margolis at the University of North Carolina at Chapel Hill, tested the ability of valproic acid to reduce the number of infected dormant cells.

Four patients on standard therapy were given the pills to take twice daily for three months. The size of this pool of infected dormant cells decreased by 75 percent in three out of the four patients, the study found.

"This finding, though not definitive, suggests that new approaches will allow the cure of HIV in the future," Margolis said. "It's a significant conceptual move forward."

Margolis said he believes the drug reactivates the virus inside a dormant cell, either waking up the cell with it or killing it.

Dr. Jean-Pierre Routy, a professor at McGill University in Montreal, Canada, who also studies the dormant HIV issue, said Margolis' results were an impressive first try.

"It's enormous for just three months' treatment to have such an effect," he said, adding that the findings merit urgent further study. "I think it's very exciting news."

However, other experts were less optimistic.

"It's extremely unlikely that this approach would work," said Dr. Robert Siliciano, a professor of medicine at Johns Hopkins University who was one of the scientists who discovered the dormant infection problem in the mid-1990s. "It assumes something about the mechanism which we don't know is true. The mechanism may involve other issues that are not affected by this drug."

"It didn't get all the cells. That's probably because it's not really targeting the right mechanism for latency," Siliciano said. "It's got to be a 99.9999 percent reduction to be useful. When you stop the drugs the virus explodes back so quickly, even if you had one latently infected cell left, in a matter of days you would be back to where you started from."

Siliciano said he also doubts the valproic acid approach will solve the problem because it's likely HIV lies dormant in other types of cells that scientists have not discovered yet and tackling those reservoirs may require a completely different approach.

"It's a little bit premature to be talking about a cure for HIV," he said.

 

German scientists discover new HIV weakness

German researchers say they’ve discovered a key peptide that prevents HIV from assembling its protective outer coating, which leaves the virus incapable of latching onto and infecting other immune system cells, Deutsche Presse-Agentur reports. The peptide was completely effective in lab tests at preventing HIV from assembling its outer membrane, but it cannot be used in its present form as an anti-HIV drug or vaccine because of difficulties in getting the peptide into HIV-infected immune system cells in the body. However, scientists hope to use their discovery as the foundation for research into new drugs that will affect the virus’s ability to form its outer membrane. Their full study appears in the online edition of the journal Nature Structural and Molecular Biology.

 

 

Gilead Says HIV Combo Pill Again Fails to Work As Well As Separate Treatments

 

FOSTER CITY, Calif. (AP) -- Gilead Sciences Inc. said Tuesday that a second study of its proposed all-in-one, once-a-day HIV pill failed to show that the combination treatment worked as well as taking the included drugs separately.

In addition, Gilead pushed back its filing timetable for the drug, sending shares down nearly 5 percent after-hours to $40.72.

Gilead and Bristol-Myers Squibb Co. announced in December that they would develop a fixed-dose pill combining Gilead's Truvada drug with Bristol-Myers Squibb's Sustiva that could potentially eliminate the need for AIDS patients to take as many as four pills a day. Truvada itself is a combination of two common HIV drugs -- Emtriva and Viread.

However, Gilead said in April that their first try at the combo pill did not work as well as the separate drugs and said it would proceed to test a second formulation of the drug. These most recent results show the second formulation also failed.

Gilead said Tuesday that it now plans to test up to three new formulations using a process called "bi-layer technology." The company plans to start these studies over the next several months.

Due to the latest data, Gilead and Bristol-Myers don't intend to submit an application for the treatment to the Food and Drug Administration until the first half of 2006, assuming positive results from the new studies. Previously, Gilead had predicted a submission before the end of 2005.

Bristol Myers shares were unchanged in recent after-hours trading, having closed earlier up 32 cents at $25.11 on the New York Stock Exchange. The pharmaceutical company is much less dependent on the collaboration than smaller Gilead, which makes most of its revenue from its HIV drugs.

 

Poor AIDS treatment fails SAfrica rape victims -study

JOHANNESBURG (Reuters) - Poor health services and training are failing many rape victims in South Africa, meaning many do not complete treatment designed to prevent them contracting HIV, a new study says.

South Africa has the world's highest HIV/AIDS caseload with one in nine people infected, adding the fear of infection to the trauma of around 50,000 people who are raped every year.

Gauteng, South Africa's richest province and home to both Johannesburg and Pretoria, commissioned the report in 2003 when the provincial health department estimated that only 16 percent of rape victims saw through their anti-retroviral treatment.

Gauteng had improved its post-rape treatment completion rates since the study was completed, but still barely half of rape victims completed their treatment in the province, provincial health officials said.

Lisa Vetten, co-author of the study conducted over eight months at 30 clinics in the province, said the low completion rates could often be blamed on ill-equipped staff at public clinics as well as the complexity and duration of treatment.

The report recommended better training for medical staff to help them deal better with rape victims and explain clearly to them how to administer the treatment.

"They're obviously in shock. It's a lot to absorb -- the prevention of infections, pregnancy, anti-biotics to prevent other STDs (sexually transmitted diseases) besides HIV/AIDS," said Vetten, gender programme manager at the Centre for the Study of Violence and Reconciliation.

But Vetten said that as the richest province, Gauteng was probably in a better position than most of South Africa's other eight provinces where health services are often rudimentary or virtually inaccessible.

Over 5 million South Africans are HIV-positive, but efforts to battle the epidemic have been hampered by medical staff shortages and deteriorating health infrastructure.

Only around 42,000 South Africans are currently receiving ARVs out of the roughly 700,000 in need of treatment.

 

HIV: an ever-changing epidemic

12 Aug 2005, 14:41 GMT - After years of decreasing numbers of new infections, HIV diagnosis is now increasing again. Ironically, it is the advancements in HIV treatment that are being cited by some as being behind the increase. While a blase attitude may have led to increased 'risk behavior', Datamonitor research suggests that a new significant step forward in HIV treatment may be seen within a decade.Despite awareness campaigns, the number of new HIV infections has increased significantly in many regions, particularly in east Asia, eastern Europe and central Asia. In addition, both the UK and Germany have experienced a rise in reported HIV incidence, largely driven by increased diagnosis and immigration from areas of high prevalence. More alarmingly, the perception that HIV is no longer a death sentence but a manageable chronic condition, has led to a rise in risk behavior in some populations.

Demographically, the epidemic has undergone significant changes over the last five to 10 years. For example, the average age of new diagnoses in France is climbing, being approximately 40-45 years old, compared to 34-37 in 1990. Furthermore, an increasing proportion of the HIV population are women, with heterosexual contact being the most common route of transmission in the majority of the seven major markets.

With these changes come new considerations for drug therapy, such as the possibility of pregnancy and prevention of mother-to-child transmission (MTCT) and potential drug interactions with products commonly used for age-related illnesses, such as hypertension and metabolic diseases.

Historically strong growth

The HIV market has historically experienced relatively strong growth, which has primarily been driven by the launch of new, more convenient antiretrovirals, such as the fixed dose combination (FDC) nucleoside reverse transcriptase inhibitors (NRTIs) and the first once-daily protease inhibitor (PI), Bristol-Myers Squibb's Reyataz (atazanavir). As such, the market for first-line naive patients is now a battleground where simplicity wins. Indeed, even older flagship products such as GlaxoSmithKline's Combivir are under threat, with some physicians expecting the newer, once-daily FDCs - Gilead's Truvada (tenofovir/emtricitabine) and GSK's Epzicom (lamivudine/abacavir) - to replace it in therapy.

The treatment-experienced market has also undergone significant changes over the last five years, with Roche's Fuzeon (enfuvirtide) being launched in 2003 for use in salvage therapy. The approval and launch of Boehringer Ingelheim's Aptivus (tipranavir) in the US in June 2005 has further increased the options for the heavily-treated patient population, with promising data regarding the use of both Aptivus and Fuzeon in combination presented at the recent third International AIDS Society (IAS) conference on HIV pathogenesis and treatment. Datamonitor expects Fuzeon to experience a compound annual growth rate (CAGR) of 11.8% between 2005 and 2010, and peak sales of $400 million by 2010, largely driven by use in such combinations.

NRTIs - backbone drugs remain dominant

The NRTI class accounted for 55%, or $3.7 billion, of sales value in 2004, making it the predominant and fastest growing antiretroviral class. This strong growth can be primarily attributed to two relatively new drugs - GSK's Trizivir (lamivudine/zidovudine/abacavir) and Gilead's Viread (tenofovir), which generated $574 million and $739 million of sales in 2004, respectively.

However, despite the impressive performance by these two drugs, the class leader remains the traditional therapeutic backbone - Combivir, an FDC of Retrovir (zidovudine) and Epivir (lamivudine), commonly used in first-line therapy. Indeed, the product has witnessed steady growth since its launch in 1997, generating $914 million of sales in 2004, representing an increase of 6.6% compared to 2003.

The launch of two new FDCs in 2004 is expected to challenge the dominance of Combivir as the favored NRTI backbone. Truvada, which combines Viread with Gilead's second antiretroviral Emtriva (emtricitabine) has experienced rapid uptake since its first launch in the US in August 2004. Key benefits of this drug include the potency and good resistance profile associated with Viread, and once-daily, single tablet dosing. Similarly Epzicom, GSK's latest FDC combining Epivir with Ziagen (abacavir), also offers once-daily, single tablet dosing. However, Ziagen is associated with a range of side effects, including the potentially fatal hypersensitivity reaction (HSR) and this has precluded switching by some physicians.

Comparative trials of Combivir, Truvada and Epzicom have demonstrated the superior efficacy of Truvada versus Combivir and equivalence between the two GSK products. However, Epzicom offers advantages in terms of convenience, being once-daily compared to Combivir's twice-daily regime, resistance and side effect profile, with HSR the main adverse event concern for Epzicom. Consequently, many physicians believe that Combivir's class and market dominance will be challenged over the next five to 10 years.

As such, Datamonitor expects Combivir sales to decline over the next 10 years, falling to $550 million by 2014, an average annual decline of 5.5% from 2005-14. In contrast, Epzicom is expected to experience relatively strong growth - a 2005-14 CAGR of 9.9% - reaching peak sales of $490 million in 2009. However, Datamonitor believes that Truvada will be the dominant FDC by 2015, with sales of $874 million and a CAGR of 19% between 2005 and 2014.

Options expand for treatment-experienced patient

The launch of Fuzeon in 2003 heralded a new era in antiretroviral therapy, where heavily treatment-experienced and multi-class resistant patients were given an additional, often life-extending, treatment option. Indeed, with the fall in AIDS-related mortality has come an ever-growing pool of treatment-experienced patients requiring novel therapies to manage their disease. As such, the focus of HIV R&D has shifted to concentrate on drugs with activity against resistant virus, such as the newly-approved PI Aptivus, which has demonstrated efficacy in patients with PI-resistant virus, enabling further lines of therapy after initial PI failure.

The next 10 years are expected to see significant advances in antiretroviral therapy. Several new classes of drug are currently in development, with the most promising of which - the CCR5 inhibitors - already in phase III trials. Currently consisting of three compounds - Pfizer's maraviroc, GSK's aplaviroc and Schering-Plough's vicriviroc - the CCR5 inhibitor class has generated a considerable amount of interest from both the medical community and pharmaceutical industry, with a potential treatment paradigm change being touted:

"I suppose initially they'll be like a second line or perhaps an add-on, but I think, as we get more and more experience with them and get comfortable with their long-term side effects, they potentially could be used as a substitute for first line treatment if, for one thing, they're shown to have less side effects, and otherwise be reasonably safe," says a US opinion leader

However, the drugs are currently being mainly studied in treatment-experienced patients, suggesting that, at least initially, use will be confined to this population. As such, the launch of these drugs (forecast to occur between 2007 and 2010) could feasibly negatively impact on products such as Fuzeon and Aptivus.

Nevertheless, with Roche planning to study combinations of Fuzeon with the novel entry inhibitors, such as the CCR5 inhibitors, the number of therapeutic options for treatment-experienced and salvage patients is expected to increase significantly. This will lead to a greater number of these patients remaining on therapy and, therefore, surviving for longer.

 

Source: Datamonitor Expert View

 

Feds Say Half of Gay Men Who Have HIV Don't Know It, Notes AHF

LOS ANGELES, Aug. 11 /PRNewswire/ -- A recent Centers for Disease Control and Prevention (CDC) study on HIV prevalence among men who have sex with men
(MSM), found that a staggering 48% of gay and bi-sexual men who were found to be HIV positive during the study were previously unaware of their HIV infection, according to a report on the study published in this week's issue of the Journal of American Medical Association (JAMA, Vol. 294, No. 6, August 10, 2005). 

The JAMA report included HIV prevalence data from the study (which took place from June 2004 through April 2005 in five US cities) from the CDC's Morbidity and Mortality Weekly Report (MMWR).  AIDS Healthcare Foundation (AHF), the nation's largest AIDS organization with AIDS treatment clinics in the US, Africa, Asia and Central America, expressed alarm over these high numbers and called for an immediate and far-reaching overhaul to the current "broken" HIV testing system in the US including widespread efforts to make HIV testing more accessible overall throughout the country.


    "The fact that almost half of the gay men who tested HIV positive during this study had no idea they were infected with HIV underscores the sad reality that the HIV testing system in this country is broken and needs to fixed," said Michael Weinstein, President of AIDS Healthcare Foundation (AHF).  "We need to normalize HIV testing and incorporate testing as a routine part of healthcare screenings in most healthcare settings.  Testing and outreach also needs to become more easily accessible to the public, particularly to those in high-risk groups such as men who have sex with men."


    During June 2004 -- April 2005, participants in five of seventeen National HIV Behavioral Surveillance (NHBS) system cities (Baltimore, Maryland; Los Angeles, California; Miami, Florida; New York, New York; and San Francisco, California) were tested for HIV infection after informed consent.  A total of 2,261 men culled from 258 venues located throughout the five cities participated in the study, titled, "HIV Prevalence, Unrecognized Infection, and HIV Testing Among Men Who Have Sex With Men -- Five U.S. Cities, June 2004 -- April 2005."

    Among the study's findings:

     *  ...of the MSM surveyed, 25% were infected with HIV, and 48% of those infected were unaware of their infection.

     *  In the five cities, 2,261 men sampled from 258 venues participated  in NHBS.  The participation rate among eligible men was 83% (range by city: 69%-99%).  A total of 1,767 (78%) were men who had one or more male sex partners and agreed to the survey, HIV test, and STARHS test (range by city: 222-462).  Of these 1,767 participants, the median age was 32 years (range: 18-81 years); 35% were white, 27% Hispanic, 25% black, 7% multiracial/other, and 6% Asian/Pacific Islander.  Participants were recruited at bars (30%), street locations (20%), dance clubs (19%), cafes/retail stores (10%), Gay Pride events (6%), social organizations (5%), gyms (5%), sex establishments (3%), and parks (1%).

     *  Of the 450 HIV-infected MSM, 217 (48%) were unaware of their HIV  infections.  The proportion of unrecognized HIV infection was highest among MSM who were aged <30 years, nonwhite, and surveyed in the four cities other than San Francisco.  Of the 217 MSM with unrecognized HIV infections, 64% were black, 18% Hispanic, 11% white, and 6%  multiracial/other.  The majority (184 [84%]) of the 217 MSM with  unrecognized HIV infection had previously been tested for HIV; 145 (79%) reported that their most recent test result was negative, 33 (18%) were unknown, and six (3%) were indeterminate.  Approximately 58% of MSM with unrecognized infections had not been tested during the preceding year.

     *  Nearly all participants (92%) reported previously being tested for HIV, and 64% reported being tested during the preceding year.  MSM  were more likely to have been tested during the preceding year if they had visited a health-care provider and their provider recommended an HIV test.

    The study's authors concluded that to decrease HIV transmission, men who have sex with men should be encouraged to receive an HIV test at least annually, and prevention programs should improve means of reaching persons unaware of their HIV status, especially those in populations disproportionately at risk.


    "In June, the CDC reported that the number of people living with HIV/AIDS in the United States had reached 1 million for the first time ever," added AHF's Weinstein.  "That number reflects a continued increase in new HIV infections -- about 40,000 new HIV cases per year and 18,000 AIDS deaths -- for a net gain of 22,000 cases each year.  Sadly, that 40,000 figure has remained constant for more than a decade, despite a 2001 pledge by the CDC that it would strive to halve the rate.  These startling numbers, both the one million overall living with HIV/AIDS and the 48% of MSM testing positive who were unaware of their infection, clearly show that we need to rethink and revamp our HIV testing and prevention strategies both on a local and national level."


SOURCE AIDS Healthcare Foundation

  

HIV-meth combo injures brain, study says
      

      Tom Musbach, PlanetOut Network
      Friday, August 12, 2005 / 12:28 PM

SUMMARY: Adding to the list of dangers of crystal meth, new research has uncovered signs of brain damage in HIV+ people who abuse the drug.

 

Adding to the list of dangers of crystal meth for some gay men, new research has uncovered signs of brain damage in HIV-positive people who abuse the drug.

Published in the August issue of the American Journal of Psychiatry, the research shows that HIV infection and methamphetamine abuse can change the size of certain brain structures, which can manifest difficulties in learning, solving problems, maintaining attention and quickly processing information.

Researchers, led by Dr. Terry Jernigan of the HIV Neurobehavioral Research Center of the University of California-San Diego, found that meth abuse inflames parts of the brain that help people understand (parietal cortex) and coordinate movements and motivation (basal ganglia).

HIV infection, on the other hand, is associated with volume losses in the parts that involve reasoning (cerebral cortex) and memory and learning (hippocampus, basal ganglia).

The study involved 103 adults divided into four groups: HIV-positive meth abusers, HIV-positive nonabusers, HIV-negative meth abusers and HIV-negative nonabusers.

"In HIV-infected people, the cognitive impairments are associated with decreased employment and vocational abilities, difficulties with medication management, impaired driving performance and problems with general activities of daily living, such as managing money," Jernigan said, according to a press release from the National Institutes of Health.

The findings add another layer of danger to repeated meth use, which has been shown to increase chances for HIV infection by impairing judgment about risky sexual behavior. The highly addictive substance, which is a popular party drug in the gay community, can eventually rot teeth, induce depression and destroy livelihoods.

Dan Carlson, co-founder of the HIV Forum, a grassroots group aimed at preventing HIV transmission among gay and bisexual men in New York City, said he is not surprised by the research.

"We have known for some time that HIV and crystal meth are toxic to the brain," he said via e-mail to the PlanetOut Network. "This research provides greater detail about how crystal harms the brain and takes the next step in outlining real-life ramifications of use, such as impaired memory and the inability to focus."

Carlson added the findings underscore the need for more effective prevention efforts.

"We have to do what we can to de-glamorize this drug and implore with gay men that using this drug can change the course of their lives," he said.

AIDSmeds.com founder Peter Staley, who personally launched the provocative "Buy crystal, get HIV free!" campaign in New York, agreed the new findings alone will not be much of a deterrent.

"Unfortunately, I'm not sure people worry enough about possible future health risks, like brain damage, when choosing their party drugs," Staley said. "For instance, most of us have tried cigarettes at least once in our lives, even though they kill more Americans than any other substance."

"Personally, I'm convinced my prior meth use has affected by memory and attention skills," said Staley, who is HIV-positive. "And most of my friends in recovery feel the same way."

 


[Home]  [Previous news]